Current Organic Chemistry - Volume 11, Issue 4, 2007

The current issue is Part I of the first thematic issue of Current Organic Chemistry devoted to Bioorganic Chemistry, a field the importance of which is nowadays self-evident. It consists of four extensive review articles dealing with the chemistry and enzymology of steroids, nucleosides and oligonucleotides. I believe that these articles are of considerable general interest and that they at the same time constitute a compilation of literature useful both for specialists working on related subjects and for newcomers entering these particular fields. Prof Mikhailopulo presents a survey of chemo-enzymatic methods applicable to preparation of structurally modified nucleosides of biological importance. Approaches utilizing whole cells, purified enzymes from wild-type bacteria and recombinant enzymes are covered. Increasing use of structurally modified oligonucleotides as tools for cell biology research and drug discovery creates increasing demand for large scale synthesis of modified nucleosides. Enzymatic methods in many cases offer at least a partial answer to this challenge. The contribution of Prof Mikhailov and coworkers gives an overview of the chemistry of disaccharide nucleosides. These interesting molecules are naturally occurring, being found as constituents of tRNA, antibiotics and other physiologically active compounds. Their structural chemistry, synthesis of and incorporation into oligonucleotides are discussed. The third review, contributed by Prof Lesnikowski, summarizes the techniques available for introduction of metal ion binding centers into oligonucleostides and gives illustrative examples of the versatile applications of such conjugates, including their utilization as electrochemical sensors, luminescent probes, artificial nucleases and constituents of nano-scale devices. The last article, from the group of Prof Wähälä, reviews the recent achievements in synthesis of estrone and estradiol steroids. Main attention is paid to reactions allowing attachment of a carbon chain directly to the carbon skeleton of the parent steroid ring system and to conversion of non-estranoid precursors to substituted estrone or estradiol derivatives. Finally, I thank all the authors for their thorough work, the results of which will undoubtedly benefit many orgaric chemists.

A survey of the chemo-enzymatic methodology for the preparation of nucleosides of biological importance is presented. The emphasis is made on the enzymatic transglycosylation and glycosylation employing the nucleoside phosphorylases and N-deoxyribosyltransferases. Application of the whole cells as biocatalysts as well as purified enzymes from wild-type bacteria and recombinant enzymes is considered.

The review summarizes structural features, biological activity and synthetic methods of disaccharide nucleosides. In the first part the structures of natural disaccharide nucleosides are presented. The consequent part deals with general methods of synthesis of these compounds - formation of new N-and O-glycosidic bonds. Recent achievements in the preparation of disaccharide nucleosides from natural nucleosides are discussed. The last part is devoted to the synthesis and properties of oligonucleotides containing disaccharide nucleosides.

A productive approach for the incorporation of metal centers into nucleic acids providing new materials must be versatile, modular and synthetically simple. Metal complex-containing DNA-oligomers are predominantly constructed via three major pathways: a) the synthesis of a chelator-containing oligonucleotide followed by metal complexation, b) the synthesis of an end-functionalized oligonucleotide to which a metal complex can be conjugated, and c) the synthesis of nucleoside/metal complex conjugates followed by incorporation of the metal bearing synthon into DNA using automated DNA synthesis on solid support. Representative examples of these methodologies are described together with brief account of selected practical applications of metal bearing DNA-oligomers.

Recent work is reviewed concerning the synthesis of estrone or estradiol homologues, of interest in diagnostics, drug discovery research etc. The survey is limited to reactions where a carbon atom or a carbon chain becomes directly attached to the steroid ring system. Also conversions of non-estranoid starting materials to substituted estrone/estradiol derivatives are discussed. The organization of the review follows steroid numbering.